Covid19, SARS-CoV Infection
Conditions
Brief summary
The purpose of this study is to test whether Fisetin, a senolytic drug, can assist in preventing an increase in the disease's progression and alleviate complications of coronavirus due to an excessive inflammatory reaction.
Detailed description
This study is a pilot, randomized, placebo-controlled, single-center study of Fisetin in elderly nursing home participants with non-, mildly-, or moderately-symptomatic and confirmed SARS-CoV-2 infection.
Interventions
DRUGFisetin
\ 20 mg/kg/day oral, NG or D tube course for 2 consecutive days twice (Days 0 & 1 and Days 8 & 9)
DRUGPlacebo
Placebo looks exactly like the treatment drug, but it contains no active ingredient
Sponsors
National Institute on Aging (NIA)
Mayo Clinic
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
65 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Men or post-menopausal women age ≥65 years. 2. Current nursing home resident. 3. CoV severity of moderate or less OR SpO2 ≥ 85% (on room air or ≤ 2 L of supplemental oxygen) at time of enrollment. 4. SARS-CoV-2 infection confirmed by mRNA-PCR test at Mayo Clinic or other CLIA certified laboratory, within 10 days before randomization. 5. Willing and able to provide written informed consent or have a legally authorized representative (LAR) who will provide informed consent.
Exclusion criteria
1. Presence of any condition that the Investigator or the subject's attending physician, physician's assistant, or nurse-practitioner believes would put the subject at risk or would preclude the patient from successfully completing the trial. 2. Pregnancy (note that only post-menopausal women will be enrolled). 3. Total bilirubin \>3X upper limit of normal or as per clinical judgment. 4. Serum aspartate transaminase (AST) or alanine aminotransferase (ALT) \>4x the upper limits of normal or as per clinical judgment. 5. Hemoglobin \<7 g/dL; white blood cell count ≤2,000/mm3 (≤2.0 x 109/L) or ≥20,000/mm3 (≥20 x 109/L); platelet count ≤ 25,000/μL (≤25 x 109/L); absolute neutrophil count ≤1 x 109/L; lymphocyte count \<0.3 x 109/L at screening or as per clinical judgment. 6. Unstable (as per clinical judgment) major cardiovascular, renal, endocrine, immunological, or hepatic disorder. 7. eGFR \<25 ml/ min/ 1.73 m2 or as per clinical judgment. 8. Plasma and/or serum glucose \>300 or as per clinical judgment. 9. Human immunodeficiency virus infection. 10. Known active hepatitis B or C infection. 11. Invasive fungal infection. 12. Uncontrolled (as per clinical judgment) pleural/pericardial effusions or ascites. 13. History of diverticulitis or diverticulosis with GI bleeding, as per clinical judgment. 14. New/active invasive cancer except non-melanoma skin cancers as per clinical judgment. 15. Known condition associated with major immunodeficiency as per clinical judgment. 16. Known hypersensitivity or allergy to Fisetin. 17. Subjects taking any of the medications listed in the Investigator Brochure may participate if they are otherwise eligible AND the medication can be safely held during the following times: * Immediately before the 1st IP administration (Day 0) until at least 10 hours after the 2nd IP administration (Day 1) * Immediately before the 3rd IP administration (Day 8) until at least 10 hours after the 4th IP administration (Day 9) 18. Participation in other clinical trials involving treatment for COVID-19 (unless reviewed and approved by the Principle Investigator.) Note that institutional standard of care treatment of COVID-19 including glucocorticoids, hydroxychloroquine, azithromycin, remdesivir, anti-spike antibodies, and/or convalescent plasma are not excluded from the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in COVID-19 Severity | Baseline, Day 2, 8, 10, 14, 30, 90 and 180 | The Ordinal Scale for Clinical Improvement was used to assess change in COVID-19 Severity. The scale has a minimum value of 0 (no clinical or virological evidence of infection) and a maximum value of 8 (death) with higher scores indicating a worse outcome. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment Group Subjects received treatment drug (Fisetin)
Fisetin: \
20 mg/kg/day oral, NG or D tube course for 2 consecutive days twice (Days 0 & 1 and Days 8 & 9) | 10 |
| Placebo Group Subjects received placebo
Placebo: Placebo looks exactly like the treatment drug, but it contains no active ingredient | 10 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Protocol Violation | 1 | 1 |
| Overall Study | Withdrawal by Subject | 2 | 0 |
Baseline characteristics
| Characteristic | Treatment Group | Total | Placebo Group |
|---|---|---|---|
| Age, Continuous | 82.8 years STANDARD_DEVIATION 7.36 | 80.55 years STANDARD_DEVIATION 8.03 | 78.3 years STANDARD_DEVIATION 8.05 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 9 Participants | 19 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 10 Participants | 19 Participants | 9 Participants |
| Region of Enrollment United States | 10 participants | 20 participants | 10 participants |
| Sex: Female, Male Female | 5 Participants | 11 Participants | 6 Participants |
| Sex: Female, Male Male | 5 Participants | 9 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 10 |
| other Total, other adverse events | 7 / 10 | 9 / 10 |
| serious Total, serious adverse events | 1 / 10 | 1 / 10 |
Outcome results
Primary
Change in COVID-19 Severity
The Ordinal Scale for Clinical Improvement was used to assess change in COVID-19 Severity. The scale has a minimum value of 0 (no clinical or virological evidence of infection) and a maximum value of 8 (death) with higher scores indicating a worse outcome.
Time frame: Baseline, Day 2, 8, 10, 14, 30, 90 and 180
Population: Data was not collected or analyzed for 1 subject in the treatment arm at day 8, day 10 and day 14 due to subject withdrawal. Data was not collected or analyzed for 2 subjects in the treatment arm at day 30, day 90 and day 180 due to subject withdrawal.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment Group | Change in COVID-19 Severity | Baseline to Day 10 | 2 score on a scale | Standard Deviation 0 |
| Treatment Group | Change in COVID-19 Severity | Baseline to Day 30 | 2 score on a scale | Standard Deviation 0 |
| Treatment Group | Change in COVID-19 Severity | Baseline to Day 8 | 2 score on a scale | Standard Deviation 0 |
| Treatment Group | Change in COVID-19 Severity | Baseline to Day 90 | 2 score on a scale | Standard Deviation 0 |
| Treatment Group | Change in COVID-19 Severity | Baseline to Day 14 | 2 score on a scale | Standard Deviation 0 |
| Treatment Group | Change in COVID-19 Severity | Baseline to Day 180 | 2 score on a scale | Standard Deviation 0 |
| Treatment Group | Change in COVID-19 Severity | Baseline to Day 2 | 1.88 score on a scale | Standard Deviation 0.31 |
| Placebo Group | Change in COVID-19 Severity | Baseline to Day 180 | 2 score on a scale | Standard Deviation 0 |
| Placebo Group | Change in COVID-19 Severity | Baseline to Day 2 | 2 score on a scale | Standard Deviation 0 |
| Placebo Group | Change in COVID-19 Severity | Baseline to Day 8 | 2 score on a scale | Standard Deviation 0 |
| Placebo Group | Change in COVID-19 Severity | Baseline to Day 10 | 2 score on a scale | Standard Deviation 0 |
| Placebo Group | Change in COVID-19 Severity | Baseline to Day 14 | 2 score on a scale | Standard Deviation 0 |
| Placebo Group | Change in COVID-19 Severity | Baseline to Day 30 | 2 score on a scale | Standard Deviation 0 |
| Placebo Group | Change in COVID-19 Severity | Baseline to Day 90 | 2 score on a scale | Standard Deviation 0 |